Talc-free polyvinyl alcohol composition

ABSTRACT

The present invention provides a talc-free composition characterizable as non-tacky and having an average water vapor permeability of at most 5.0 times 10 −7  grams per Pascal-hour-meter and having a capability of forming a non-tacky film having an average water vapor permeability of at most 5.0 times 10 −7  grams per Pascal-hour-meter. Also provided are the non-tacky film, a method of coating a dosage form with the composition, and a manufactured article comprising the composition.

FIELD

The invention generally relates to a non-tacky talc-free composition,the non-tacky film, manufactured article comprising the composition, anda method of coating a dosage form with the composition.

BACKGROUND

Talc-containing coatings of pharmaceutical and nutraceutical dosageforms are currently in commercial use. The talc desirably imparts a lowtack or tack-free property to the coatings, enabling faster packagingand providing cleaner process (no tablet dust generation) duringmanufacturing, and making dosage forms easier for patients to handle andswallow. For example, talc is used to reduce tackiness in a commercialPVOH-based coating, OPADRY II (Colorcon, Inc., Harleysville, Pa.; BPSIHoldings LLC, Wilmington Del., both of USA).

Some coatings of pharmaceutical or nutraceutical dosage forms are knownthat supposedly do not require talc, although they may desirably employtalc in preferred embodiments. Some, but not all, of these coatingsemploy polyvinyl alcohol (PVOH) or carboxymethylcellulose (CMC), but notboth, as a film-forming agent. For example, see WO 2009/031039 A2 andU.S. 2010/0062062 A1. WO 2009/031039 A2 mentions using particularmolecular weight-modified CMC coating materials either alone or incombination with other types of hydrocolloids, biogums, celluloseethers, and the like. In addition to the above essential modified CMCcoating agents, the coating materials may also comprise other additionalfilm-forming agents other than the hydrocolloids, cellulose ethers,and/or biogums. U.S. 2010/0062062 A1 mentions, among other things,compressing a mixture of selected excipients and PVOH-coated drugpowders or particulates into tablets. The compressing of the coated drugpowders or particulates into tablets therefore requires the coatingsthereof to adhere or stick to each other, the excipients, or both insuch a way so as to form the tablet. Thus in U.S. 2010/0062062 A1, thePVOH coating undesirably is tacky.

A problem addressed by the present invention includes providing atalc-free composition that is characterizable as non-tacky and havinglow water vapor permeability.

BRIEF SUMMARY OF THE INVENTION

The present inventors recognized that talc opaques and whitens coatings,which is undesirable for some dosage form applications that requirecoatings that are colored, clear, or both. The inventors also recognizedthat coatings comprising PVOH alone or CMC alone independently have oneor more drawbacks comprising being tacky, opaque, colored, permeable towater vapor, or a combination thereof. They found the coatings of PVOHalone to be at least tacky and the coatings of CMC alone to be at leasthazy and unacceptably permeable to water vapor. The inventorsunexpectedly discovered a talc-free composition that is characterizableas non-tacky and having low water vapor permeability. In preferredembodiments the talc-free composition is also substantially clear,hazeless, or a combination thereof. In some embodiments the talc-freecomposition is also colorless unless a separate color additive (e.g.,pigment or dye) has been added thereto.

In a first embodiment the present invention provides a talc-freecomposition characterizable as non-tacky and having an average watervapor permeability of at most 5.0 times 10⁻⁷ (0.0000005) grams perPascal-hour-meter (g/Pa.h.m) and having a capability of forming anon-tacky film having an average water vapor permeability of at most 5.0times 10⁻⁷ g/Pa.h.m.

Preferably, the non-tacky film prepared from the talc-free compositionfurther has at least one of properties (a) and (b): (a) a normalizedfilm clarity of at least 500 percent per millimeter of film thickness(%/mm); and (b) a film haze of at most 13 percent. In other embodimentsproperty (b) is a normalized film haze of at most 250 percent permillimeter of film thickness (%/mm), preferably at most 180%/mm, morepreferably at most 120%/mm, still more preferably at most 80%/mm, evenmore preferably at most 25%/mm, and yet more preferably at most 13%/mmof film thickness (%/mm). At film thicknesses typically employed incommercial solid dosage coating applications (e.g., pharmaceutical,nutraceutical, and veterinarian applications), the invention non-tackyfilm would have a haze of at most 13%. In some embodiments the talc-freecomposition at least comprises property (a), in other embodiments atleast property (b), and still other embodiments both properties (a) and(b).

In a second embodiment the present invention provides a method ofpreparing a coated solid dosage form, the method comprising contacting acoating-effective amount of the talc-free composition with a solidhealth formulation comprising an active ingredient, the contacting beingperformed in such a way so as to coat the solid health formulation togive a coated solid dosage form comprising a non-tacky film comprisingthe talc-free composition, the non-tacky film being in coating operativecontact with the solid health formulation and having an average waterpermeability of at most 5.0 times 10⁻⁷ grams per Pascal-hour-meter.Preferably, the coating operative contact means the non-tacky filmcompletely covers the surface of the solid dosage form.

In a third embodiment the present invention provides a manufacturedarticle comprising the talc-free composition. Preferably, themanufactured article comprises the coated solid dosage form.

In another embodiment the present invention provides the non-tacky filmcomprising the talc-free composition.

The invention compositions are useful, for example, as binders for wetgranulation of solid health formulations; a coating or film forpreparing coated solid dosage forms, especially of pharmaceutical,veterinary, and nutraceutical dosage forms (collectively referred toherein as dosage forms). For example, the invention compositions can beused to coat nutraceutical tablets to give coated tablets, whereconsumers prefer their nutraceutical tablets to look natural; to producea gloss on pharmaceutical or veterinary tablets; and to prepare clear orcolored coatings. The colored coatings would desirably impart aestheticand tailorable light-blocking functionalities to the dosage forms andcould be used to distinguish between different dosage strengths. Theinvention composition is also useful in other applications such asadhesive, sizing (e.g., textile and paper sizing), and solutionemulsifying, suspending, and thickening applications.

Advantageously, the invention provides a talc-free composition capableof forming a non-tacky film or coating having an average water vaporpermeability of at most 5.0 times 10⁻⁷ g/Pa.h.m. In preferredembodiments the talc-free composition has at least one of theaforementioned properties (a) and (b), and more preferably bothproperties (a) and (b). Additional advantages can include the filmreduces tackiness during tablet coating methods such that the coatedtablets do not agglomerate, improves visual film appearance (e.g.,reduction in film defects (e.g., cracking) compared to talc-containingnon-invention coatings, and shortens time required for coating tablets.

Additional invention embodiments are described in the remainder of thespecification, including the claims.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments of the present invention summarized previously and theAbstract are incorporated here by reference. As used herein, the term“active ingredient” means any compound or substance that is intended toprovide a health benefit in a nutraceutical, pharmaceutical orveterinary context. The term “coated” means having a surface covering orfilm. The term “coating-effective amount” means a quantity sufficient tocover as by forming a film. The term “coating operative contact” means asurface covering that indirectly (via an intermediate material) or,preferably, directly physically touches, preferably substantially theentire surface. The term “composition” means the qualitative andquantitative make-up of a chemical substance and includes homogeneousand heterogeneous substances. The term “contacting” (as in contactingwith) and the like means causing a coming together or touching. The term“dosage form” means a physical shape or structure suitable foradministration of-the active ingredient therein to a human or animal.The term “coated solid dosage form” means a film-covered variant of ahealth formulation having a definite shape and volume (as opposed tobeing “fluid”). The term “health formulation” means a preparation of atleast an active ingredient and at least one other ingredient orcomponent that is suitable for use in a nutraceutical, pharmaceutical orveterinary context. The term “film” means a thin covering, typicallyhaving a thickness of at most 1.0 millimeter (mm). The term“manufactured article” means a member of a class of things, wherein themember is not found in nature. The term “non-tacky” means a result of“not adhering” as determined using the Tackiness Test Method describedlater. The terms “film clarity” and “normalized film clarity”respectively mean a result or a transformed result of the Film ClarityTest Method described later that is useful for comparison. The terms“film haze” and “normalized film haze” respectively mean a result or atransformed result of the Film Haze Test Method described later that isuseful for comparison. The term “operative contact” means an indirect(via an intermediate material) or, preferably, direct physical touching.The term “talc-free” means lacking the mineral composed of hydratedmagnesium silicate having the chemical formula H₂Mg₃(SiO₃)₄ orMg₃Si₄O₁₀(OH)₂. The terms “water vapor permeability” and “WVTpermeability” are synonymous and mean a result of the Water VaporTransmission Rate Test Method described later.

Conflict Resolution: what is written in the present specificationcontrols any conflict with what is written in a patent, patentapplication, or patent application publication, or a portion thereofthat is incorporated by reference. The structure controls any conflictwith a compound name. The unit value recited without parenthesescontrols any conflict with an intended corresponding unit value that isparenthetically recited.

Numerical ranges: any lower limit of a range of numbers, or anypreferred lower limit of the range, may be combined with any upper limitof the range, or any preferred upper limit of the range, to define apreferred aspect or embodiment of the range. Unless otherwise indicated,each range of numbers includes all numbers, both rational and irrationalnumbers, subsumed in that range (e.g., “from 1 to 5” includes, forexample, 1, 1.5, 2, 2.75, 3, 3.81, 4, and 5).

In some embodiments the partially closed phrase, “consisting essentiallyof” replaces the open term “comprising.” In such embodiments thetalc-free composition can include additional ingredients provided theydo not cancel the basic and novel characteristics of the presentinvention. Such basic and novel characteristics of the present inventionare the aforementioned non-tackiness and average water vaporpermeability. In some embodiments the basic and novel characteristicsalso include at least one, preferably both, of the properties (a) and(b).

Preferably, the talc-free composition comprises a low viscositypolyvinyl alcohol (LV-PVOH) and a tack-reducing organic adjuvant,wherein the weight/weight ratio of the LV-PVOH to tack-reducing organic(TRO) adjuvant in the composition is from ≧60:40 to ≦95:5. In someembodiments the LV-PVOH/TRO adjuvant wt/wt ratio is at least: 61:39, inother embodiments at least 65:35, in other embodiments at least 7:3, andin other embodiments at least 8:2. In some embodiments the LV-PVOH/TROadjuvant is at most 94:6, in other embodiments at most 91:9, in otherembodiments at most 90:10, and in other embodiments at most 8:2. In someembodiments the LV-PVOH/TRO adjuvant wt/wt ratio is 6:4, in otherembodiments 7:3, in other embodiments 8:2, in other embodiments 9:1, andin other embodiments 19:1. The terms “low viscosity polyvinyl alcohol”and “LV-PVOH” are synonymous and mean an oligomeric or polymericmaterial having repeat units derived from vinyl alcohol, a dynamicviscosity of from 2 milliPascal-seconds (mPa·s) to 10 mPa·s measuredwith a 4 weight/volume percent (wt/vol %, weight in grams (g) of LV-PVOHper volume in milliliters (mL) of deionized water) aqueous solutionthereof at 20° C.; and a saponification degree of from 80 mole percent(mol %) to 95 mol %. Preferably, the dynamic viscosity is from 3 mPa·sto 9 mPa·s, and more preferably from 3.5 mPa·s to 8 mPa·s (e.g., from 4mPa·s to 7 mPa·s), all measured with a 4 wt/vol % aqueous solutionthereof at 20° C. Preferably, the saponification degree is from 84 mol %to 92 mol %, and more preferably from 85 mol % to 90 mol % (e.g., from86.5 mol % to 89.0 mol %). The saponification degree is relevant toLV-PVOH prepared by saponifying (e.g., hydrolyzing with NaOH) theaforementioned mol % of acetate functionalities in a penultimatepolyvinyl acetate) to give the LV-PVOH and acetic acid (uponneutralization of pH), and removing the acetic acid (e.g., byevaporation).

As used herein, the term “tack-reducing organic adjuvant” or “TROadjuvant” means a material other than PVOH, wherein the materialcomprises carbon, hydrogen, and oxygen atoms, and optionally, nitrogenatoms, wherein the material functions to reduce tackiness of the LV-PVOHand, preferably, also improve at least one property of the LV-PVOH thatis a light transmission property (e.g., clarity, haze, or preferablyboth) or water vapor permeability property so as to enable afunctionality of the invention composition that is not enabled by PVOHalone. Preferably, the TRO adjuvant is a clear, non-tacky film formingorganic polymer. In some embodiments the TRO adjuvant is acarboxymethylcellulose (CMC), poly(ethylene glycol), hydroxypropylmethyl cellulose (HPMC), maltodextrin, methylcellulose, orpolyvinylpyrrolidone (PVP), or a combination thereof. More preferably,the TRO adjuvant is a CMC.

In some embodiments the talc-free composition further comprises orconsists essentially of a non-canceling amount of at least oneadditional ingredient that is a secondary organic adjuvant. The term“non-canceling amount” means a quantity that does not negate theaforementioned non-tackiness and average water vapor permeability.Preferably, the quantity also does not negative at least one of,preferably both, the properties (a) and (b). Preferably, the at leastone additional ingredient (secondary organic adjuvant) is a plasticizer,removable dispersant, surface-active agent (surfactant), or acombination of at least two thereof. In some embodiments the plasticizerand TRO adjuvant are the same ingredient, and in other embodimentsdifferent ingredients. In some . embodiments the plasticizer andremovable dispersant are the same ingredient, and in other embodimentsdifferent ingredients. In some embodiments the plasticizer andsurfactant are the same ingredient, and in other embodiments differentingredients. The term “removable dispersant” means a volatile substanceeffective for producing a suspension, solution, or combination thereofcontaining a wide distribution of the LV-PVOH and TRO adjuvant in thevolatile substance, the volatile substance having a boiling point (h.p.)below about 130 degrees Celsius (° C.) at 101 kilopascals (kPa)pressure. Preferably, the b.p. of the volatile substance is from about0° C. to about 115° C., more preferably from about 30° C. to 110° C.,and still more preferably from about 34° C. to about 105° C., all at 101kPa. Preferably, the removable dispersant is a liquid at 20° C. and 101kPa. When the talc-free composition further comprises the removabledispersant, preferably the removable dispersant is from 50 wt % to 99 wt%, and typically from 50 wt % to 98 wt % of total weight of thetalc-free composition, including weight of the removable dispersant.Preferably, the removable dispersant is a solvent effective fordissolving the talc-free composition to give a solution thereof, whereinthe solution is at a temperature useful for applying same to the solidhealth formulation. Examples of preferred removable dispersants areacetic acid, acetone, ethanol, ethyl acetate, methanol, and, morepreferably, water. The term “plasticizer” means a solid or liquidsubstance effective for increasing fluidity of the talc-freecomposition. When the talc-free composition further comprises theplasticizer, preferably the plasticizer is from 0.01 wt % to 20 wt % oftotal weight of the talc-free composition, not including weight of anyremovable dispersant. Preferably, the plasticizer is non-volatile (i.e.,has a h.p. greater than about 150 degrees Celsius (° C.) at 101 kPapressure), and substantially remains in the talc-free composition afterremoval of any removable dispersant therefrom. When employed, in someembodiments the plasticizer forms a blend with the talc-free compositionwithout covalently bonding thereto, and in other embodiments at leastsome of the plasticizer reacts to form a covalent bond (e.g., viacarboxylic acid esterification reaction) with at least some of theLV-PVOH or TRO adjuvant. Examples of preferred plasticizers areglycerol, a poly(ethylene glycol) (PEG), and lecithin. Examples ofsuitable PEGs are PEG-400, PEG-3350 and others that are commerciallyavailable from Sigma-Aldrich Company, St. Louis, Mo., USA, or The DowChemical Company, Midland, Mich., USA. For example, Dow providesCARBOWAX™ brand PEGs in number average molecular weight range of from200 g/mol to 8000 g/mol. These PEGs (average M_(n) range in g/mol)include PEG-4 (190-210), PEG-6 (285-315), PEG-8 (380-420), PEG-6/PEG-32blend, PEG-12 (570-630), PEG-20 (950-1050), PEG-32 (1305-1595), PEG-75(3015-3685), PEG-90 (3600-4400), PEG-100 (4400-4800), and PEG-180(7000-9000), wherein these PEGs are named according to the establishedPEG nomenclature of the Personal Care Products Council (formerlyCosmetics, Toiletries and Fragrances Association), Washington, D.C.,USA, using International Nomenclature Cosmetic Ingredient namingconvention. In some embodiments the talc-free composition furthercomprises the plasticizer, the TRO adjuvant is a different ingredientthan the plasticizer, and the plasticizer is a poly(ethylene glycol),preferably PEG-400. The terms “surface-active agent” and surfactant” aresynonymous and mean a substance that can reduce surface tension ofwater. When the talc-free composition further comprises the surfactant,preferably the surfactant is from 0.001 wt % to 1 wt % of total weightof the talc-free composition, not including weight of any removabledispersant. Examples of functional classifications of surfactants areemulsifiers, wetting agents, foaming agents, dispersing agents andanti-foaming agents. Examples of structural classifications ofsurfactants are ionic surfactants and nonionic surfactants. Examples ofionic surfactants are anionic surfactants (e.g., sodium laurylsulfate),cationic surfactants (e.g., cetyl trimethylammonium bromide), andzwitterionic surfactants (e.g., amino acids). Examples of nonionicsurfactants are fatty alcohols, polyoxypropylene glycol, andpolysorbates (e.g., polyoxymethylene (20) sorbitan monooleate (i.e.,polysorbate 80, which is commercially known as Tween 80)).

In some embodiments the talc-free composition further comprises glycerolor a PEG as the non-volatile plasticizer. In some embodiments thetalc-free composition further comprises glycerol or a PEG as thenon-volatile plasticizer and a polysorbate surfactant. In someembodiments the talc-free composition further comprises water as theremovable dispersant, and in other embodiments the talc-free compositionsubstantially lacks removable dispersant. In some embodiments thetalc-free composition comprises the LV-PVOH, CMC as the TRO adjuvant,and a PEG as the non-volatile plasticizer. In some embodiments thetalc-free composition comprises the LV-PVOH, CMC as the TRO adjuvant,the PEG as the non-volatile plasticizer, and a polysorbate surfactant.In some embodiments the talc-free composition comprises an aqueoussolution of the LV-PVOH, CMC, and PEG, and in other embodiments anaqueous solution of the LV-PVOH, CMC, PEG, and polysorbates. In someembodiments the talc-free composition lacks lecithin, and in otherembodiments further comprises at most a low concentration (e.g., <1weight percent (wt %)) of lecithin. In some embodiments the talc-freecomposition is as described in any one of the foregoing embodiments inthis paragraph except CMC is the only TRO adjuvant, i.e., the talc-freecomposition lacks HPMC, methylcellulose, maltodextrin, and PVP. In someembodiments the talc-free composition is as described in any one of theforegoing embodiments, but the immediately preceding one, in thisparagraph except the CMC is entirely replaced by HPMC, methylcellulose(e.g., a METHOCEL™), maltodextrin, PVP, or a combination thereof.

Preferably, the health formulation is a nutraceutical, pharmaceutical,or veterinary dosage form. Preferably, the dosage form is a unit dosageform. The health formulation can be in any physical form. Examples ofsuitable physical forms are solid and liquid-containing physical forms.

Examples of suitable solid health formulations are a bead (e.g.,nonpareil bead), powder, granule, tablet (e.g., prepared by compressingpowder), capsule (e.g., gelatin capsule or components thereof), gelcaptablet, lozenge, patch, and troche. At least some of the ingredients ofthe solid health formulation are solid ingredients. The inventioncontemplates solid health formulations that in some embodiments furthercontain a relatively small amount of at least one liquid ingredient, andin other embodiments contain only solid ingredients. Each of the solidingredient(s) of the solid health formulation can be characterized asbeing amorphous, partially crystalline, or crystalline. The inventioncomposition can be used as an ingredient in, or preferably to coat orform a film on, the solid health formulations. Examples of suitableliquid-containing health formulations are a cream, elixir, emulsion,gel, lotion, ointment, solution (e.g., in water), and syrup. Theinvention composition can be used as an ingredient in theliquid-containing health formulations.

Preferably, the active ingredient is a nutraceutically,pharmaceutically, or veterinary active ingredient. The nutraceuticallyactive ingredient provides a dietary, nutritional, or preventativehealth benefit. The active ingredient can be a solid or liquid. In someembodiments the solid health formulation comprises the liquid activeingredient widely distributed on or in a solid excipient (e.g., solidcarrier), in other embodiments a solid active ingredient widelydistributed in a liquid excipient (e.g., liquid carrier), and in stillother embodiments a solid active ingredient widely distributed in asolid excipient so as to form a blend therewith. Examples ofnutraceutically active ingredients are a dietary supplement (e.g., anantioxidant (e.g., resveratrol), flavinoid (e.g., from citrus fruit,tea, wine, or cocoa bean), herb, mineral, naturally-occurring aminoacid, and vitamin) and an enriched food (e.g., a soya protein enrichedgranola bar). The pharmaceutically or veterinary active ingredientprovides a disease treating health benefit (e.g., increases time toonset of at least one symptom in prophylactic treatment, diminishesseverity of at least one symptom in palliative treatment, or inhibitsprogression of a pathological effect in a disease modifying treatment ofa disease or disorder in a human or animal patient in need of suchtreatment. Examples of pharmaceutically or veterinary active ingredientsare an analgesic (e.g., carprofen), angiotensin converting enzyme (ACE)inhibitor (e.g., quinapril, e.g., quinapril hydrochloride), antibiotic(e.g., azithromycin), anti-convulsant (e.g., gabapentin),anti-depressant (e.g., sertraline, e.g., sertraline hydrochloride),anti-fibromyalgic (e.g., pregahalin), anti-hypertensive (e.g.,amlodipine, e.g., amlodipine besylate), and a cholesterol lowering drug(e.g., atorvastatin, e.g., atorvastatin calcium).

In some embodiments the health formulation further comprises at leastone acceptable excipient in admixture with the active ingredient. Theterm “admixture” means a product of being blended together. The term“acceptable excipient” means any compound or substance other than theactive ingredient(s) that is suitable for use in the health formulation.Preferably, the acceptable excipient is a nutraceutically,pharmaceutically, or veterinary acceptable excipient. Examples ofnutraceutically, pharmaceutically, or veterinary acceptable excipientsare carriers; diluents; stabilizers; nutraceutical, pharmaceutical, andveterinary adjuvants; and characteristic components of the dosage formsuch as capsule shells (e.g., gelatin capsule shells) for capsules andsemipermeable membranes and backings for transdermal patches.

In some embodiments the talc-free composition further comprises and themethod of preparing the coated solid dosage form further employs theremovable dispersant. The coating of the solid health formulation togive the coated solid dosage form is preferably carried out by applyinga surface-coating effective amount of a suspension or, preferably,solution of the talc-free composition in the removable dispersant (e.g.,a solvent such as ethanol or water) to an exposed surface of the (solid)health formulation in such a way so as to evenly cover the exposedsurface of the (solid) health formulation with the talc-freecomposition; and removing the removable dispersant from the covered(solid) health formulation to give the coated solid dosage form. Theterm “surface-coating effective amount” means a quantity sufficient tocover the exposed surface. Examples of applying are spraying, dipping,and tumbling. Examples of removing are evaporating, blotting, andwiping. The suspension or solution of the talc-free compositionpreferably is prepared by contacting the talc-free composition to thesuitable amount of the removable dispersant (e.g., a solvent such asethanol or water) so as to give the suspension or solution thereof.Examples of contacting are agitating, shaking, spraying, stirring, andtumbling.

Preferably, the manufactured article comprises a health formulationcomprising an active ingredient and the talc-free composition inoperative contact therewith.

Illustrative examples of the present invention are provided later wherethe examples employ certain methods and materials, which include certainpreparations. The methods and materials and preparations are describedin the following section.

LV-PVOH designated Gohsenol EG-05P from Nippon Gohsei, Osaka, Japan.Gohsenol EG-05P has a saponification degree of 86.5 mol % to 89.0 mol %and a dynamic viscosity of 4.8 mPa·s to 5.8 mPa·s measured as a 4 wt/vol% aqueous solution at 20° C.

CMC: designated Sodium Carboxy Methyl Cellulose CRT-30 PA, DS=0.9, lot7M650 from The Dow Chemical Company, Midland, Mich., USA.

PEG-400 and PEG-3350: respectively designated CARBOWAX SENTRYPolyethylene glycol 400NF, WL0101AAKC and CARBOWAX SENTRY Polyethyleneglycol 3350, from The Dow Chemical Company.

Polysorbate 80: (Tween 80) designated enzyme grade, 943317 from FisherScientific.

Tablets: designated Placebo tablets (100 g red caplet cores, 493 g whiteoval tablets, 6.5 g white disks) from The Dow Chemical Company.

Dynamic Viscosity Test Method: Measure solution viscosities using aBrookfield-II, D06719, using an appropriate spindle number 2, 3, 5, or 7and relevant 10, 20, 50 and 100 revolutions per minute (rpm).

Film preparation: Complete all film preparations and storage in aconstant temperature (22° C.) and relative humidity (50% RH)environment. Hand draw wet films (1 mm) on glass plates by slowlypouring a 20 wt % solution near an edge of a 1 mm gapped casting (drawndown) bar, and then steadily draw the solution to minimize bubbles anddefects. Dry the films on the plates for two days, remove them from theplates, and anneal the films for an additional 1 day. Measure filmproperties on the annealed film. Preferably conclude all film testingwithin 4 days of film removal to minimize any sample-to-sample variance.When not testing films, store films between sheets of paper and at theconstant temperature and relative humidity.

Film Clarity Test Method: Measure film clarity of films using a PacificScientific PG-5500 from Gardner Laboratory Inc., Bethesda, Md., USA anda Zebedee CL-100 from Zebedee Corporation, Moore, S.C., USA, calibratedwith an open port, a black standard and a Mylar film standard at 100, 0,and 87 (+/−1) percent clarity, respectively. Read clarity measurementson four different locations on each film. Record the average of the fourmeasurements.

Film Haze Test Method: Measure haze of prepared films with a Haze-gardPlus from BYK Gardner, Columbia, Md., USA, Catalog Number 4725. Reportboth haze and transmission readings as a percentage. Record an averagevalue of four readings.

Divide percent film haze and clarity values by film thickness inmillimeters to give the percent normalized film haze and percentnormalized film clarity.

Tackiness Test Method: Tablets are coated according to the ad remExamples described later. The tackiness of the coated tablets can be aqualitative visual observation of coated tablets agglomerating andsticking to each other or not agglomerating or sticking to each other.Preferably the tackiness is a quantitative weight percent equal toweight of agglomerated portion, if any, of the coated tablets as apercentage of total weight of coated tablets prepared (i.e., weight ofindividual coated tablets plus any agglomerated portion). If theagglomerated portion is <10 wt %, preferably <5 wt %, and morepreferably ≦1 wt %, and still more preferably 0 wt % (i.e., there is noagglomeration), the talc-free composition and coating of the coatedtablets are deemed to be “non-tacky” for purposes of this invention.Photograph samples to compare experimental runs.

Water Vapor Transmission Rate Test Method: Measure water vaportransmission rates using a “dry cup” method. Weigh calcium chloride (2.0g) into a 4 ounce (120 mL) jar, and allow it to sit at 50% relativehumidity (73° C.) with a closed ring cap (2.5 cm diameter hole therein)for 1 hour. Next, place a small amount of vacuum grease around the edgeof the jar's mouth. Cut films into approximately 1.3 inch (3.3centimeter (cm)) diameter circles using a metal punch. Place film samplecircle on top of the jar, and place a lid having a 1-inch (2.5 cm)diameter hole on top of the film circle. Tighten the lid to form a sealwhile making sure not to crack the film circle. Place jars into atemperature-humidity chamber equipped with an Environ-Cab controller(Lab-Line Instrument, Inc.) set to 75% relative humidity and 25° C.Record total weight of the jar, lid, films, and calcium chloride andre-measure total weight every 24 hours for 5 days. Use a linearregression of total weight gain (m) versus time (t) to obtain a masstransfer rate. Divide the mass transfer rate by the area of the exposedfilm to provide a water vapor transmission (WVT) rate in grams persquare centimeters hour (g/cm²hr),

${{WVT} = \frac{m_{t}}{A}},$

where m_(t) is the change in mass with time (grams per hour (g/hr)) andA is the exposed film area in square centimeters (cm²). Calculate thefilm permeability according to the following equation:

${{Permeability} = \frac{{WVT}*l}{S\left( {{RH}_{2} - {RH}_{1}} \right)}},$

where l is the film thickness, S is the saturated vapor pressure ofwater at 25° C., RH₂ is 0.75 (75% relative humidity) and RH₁ is 0. TheS(RH₂−RH_(J)) term is the driving force for mass transfer of waterthrough the film.

Films of the invention talc-free compositions can be favorably comparedto the following films of non-invention talc-free compositions (a) to(d):

(a) a film of 100% CMC, which film has a normalized film haze of 14%/mm,a normalized film clarity of 472%/mm, and an average WVT permeability of12 times 10⁻⁷ g/Pa.h.m;

(b) a film of 100% Gohsenol EG-05P, which film is tacky (13 wt %agglomerated portion when tablets are coated therewith according to thetablet coating procedure described later);

(c) a film of 100% Gohsenol EG-40P (a high viscosity PVOH that has asaponification degree of 86.5 mol % to 89.0 mol % and a dynamicviscosity of 40 mPa·s to 46 mPa·s measured as a 4 wt/vol % aqueoussolution at 20° C.), which film is tacky and has substantially increasednormalized film haze and decreased normalized film clarity compared tothose of film (b); and

(d) a film of 50:50 Gohsenol EG-05P/CMC, which film has an average waterpermeability of 7 times 10⁻⁷ g/Pa.h.m.

Some invention embodiments are described in more detail in the followingExamples.

EXAMPLES 1 to 6

talc-free compositions of LV-PVOH and CMC. Dissolve a total of 8 g to 25g (e.g., 10 g) of Gohsenol EG-05P (LV-PVOH) and CMC and, optionally,plasticizer according to Table 1 below in deionized (DI) water (e.g.,100 g) with mixing to give talc-free composition as a solution (4 wt %to 15 wt % solids) of each of Examples 1 to 6. Evaporate water from aportion of the solution to give a dried talc-free composition of each ofExamples 1 to 6 having Gohsenol EG-05P LV-PVOH, CMC, and, optionally,plasticizer as shown in Table 1.

TABLE 1 Examples 1 to 6 Ex. LV-PVOH CMC Ratio LV-PVOH/ Plasticizer No.(g) (g) CMC (wt/wt) (g, wt %*) 1 9.5 0.5 95:5  None 2 9.0 1.0 90:10 None3 8.0 2.0 80:20 None 4 7.0 3.0 70:30 None 5 6.0 4.0 60:40 None 6 9.0 1.090:10 PEG-400 (2.2 g, 18.0 wt %) *wt % based on total weight of LV-PVOH,CMC, and any plasticizer.

EXAMPLES A to F

Coated tablets. In separate experiments, charge a Vector Hi-Coater modelLDCS, having a temperature exhaust set point of 40° C., with tablets.Spray the solution of any one of Examples 1 to 6 at a spray rate of 2.0to 2.7 grams per minute (g/min) onto the tablets for a time periodcalculated to achieve a theoretical film weight gain of 1 to 3% to givecoated tablets of each of Examples A to F, respectively. Evaluate filmsand coated tablets for tackiness, average water permeability in gramsper Pascal-hour-meter×10⁻⁷; film thickness normalized film clarity inpercent clarity per millimeter film thickness; film haze in percent; andfilm thickness normalized film haze in percent haze per millimeter filmthickness.

TABLE 2 Examples A to F Ratio LV- Tacky Average Water Normalized FilmNormalized Ex. Composition PVOH/CMC portion Permeability Film Clarityhaze Film Haze No. Ex. No. (wt/wt) (wt %) (g/Pa · h · m) 10⁻⁷) (%/mm)(%) (%/mm) A 1 95:5  7 1.8 1013 0.1 1 B 2 90:10 4.5 1.9 861 2.1 22 C 380:20 1.8 1.5 607 10.7 114 D 4 70:30 0 1.9 545 13 174 E 5 60:40 0 1.42090 7.2 237 F 6 90:10 0.13 4.4 735 4 74

As shown by the Examples, the talc-free composition is capable offorming a non-tacky film or coating on a solid dosage form, the film orcoating unexpectedly having an advantageous combination orcharacteristics comprising an average water vapor permeability of atmost 5.0 times 10⁻⁷ g/Pa.h.m; a normalized film clarity of >500%/mm; afilm haze of ≦13%; and in some embodiments also a normalized film hazeof <13%/mm. The coated tablets have coatings comprising embodiments ofthe invention non-tack film and arc of a film thickness suitable for usein pharmaceutical, nutraceutical, and veterinarian coated tabletapplications.

1. A talc-free composition characterizable as non-tacky and having anaverage water permeability of at most 5.0 times 10⁻⁷ grams perPascal-hour-meter and having a capability of forming a non-tacky filmhaving an average water vapor permeability of at most 5.0 times 10⁻⁷grams per Pascal-hour-meter.
 2. The talc-free composition of claim 1further characterizable as having at least a normalized film clarity ofat least 500 percent per millimeter of film thickness.
 3. The talc-freecomposition of claim 1 further characterizable as having a film haze ofat most 13 percent.
 4. The talc-free composition of claim 1 consistingessentially of a low viscosity polyvinyl alcohol and a tack-reducingorganic adjuvant, wherein the weight/weight ratio of the low viscositypolyvinyl alcohol to tack-reducing organic adjuvant in the compositionis from ≧60:40 to ≦95:5.
 5. The talc-free composition of claim 4,wherein the tack-reducing organic adjuvant is a carboxymethylcellulose,poly(ethylene glycol), hydroxypropyl methyl cellulose, maltodextrin,methylcellulose, or polyvinylpyrrolidone, or a combination thereof. 6.The talc-free composition of claim 5, wherein the tack-reducing organicadjuvant is a carboxymethylcellulose.
 7. The talc-free composition ofclaim 1 further consisting essentially of a non-canceling amount of atleast one secondary organic adjuvant that is a plasticizer, surfactant,or removable dispersant.
 8. The talc-free composition of claim 7,wherein the secondary organic adjuvant is poly(ethylene glycol),polysorbate, water; or a combination of poly(ethylene glycol),polysorbate, and, optionally, water.
 9. A method of preparing a coatedsolid dosage form, the method comprising contacting a coating-effectiveamount of the talc-free composition of one of the preceding claims witha solid health formulation comprising an active ingredient, thecontacting being performed in such a way so as to coat the solid healthformulation to give a coated solid dosage form comprising a non-tackyfilm comprising the talc-free composition in coating operative contactwith the solid health formulation.
 10. A manufactured article comprisingthe talc-free composition of claim
 1. 11. The manufactured article ofclaim 10 comprising a coated solid dosage form comprising a non-tackyfilm comprising the talc-free composition, the non-tacky film being incoating operative contact with the solid health formulation and havingan average water permeability of at most 5.0 times 10⁻⁷ grams perPascal-hour-meter.
 12. A non-tacky film comprising the talc-freecomposition of claim 1.